USP <800> Engineering Controls Q&A

Thank you to all who joined us for our recent webinar on USP <800> and its impact to engineering controls!

If you didn’t get a chance to attend, the webinar is available on-demand here. A special thanks to all who asked such good questions, both before and during the webinar. We received more questions than we could answer in a one-hour webinar, so here for the benefit of all are our responses to your questions.

What are the significant differences between USP <797> and USP <800> regarding the requirements for negative pressure rooms and C-PECs?

USP <800> is meant to work in conjunction with <797>, so a lot of the regulations are harmonious. There are a few exceptions, and expect <797> to be updated with these new changes shortly. USP <800> states that the negative pressure room has to be between 0.01 and 0.03 inches of water column more negative than the surrounding areas. <797> didn’t have an upper limit. C-PECs now have to be located within a negative pressure room for all hazardous drug work. This does not have to be a CACI. The last difference is that all hazardous drug work needs to be done in a C-PEC.

Do you have to wear personal protective equipment (PPE) when transporting the hazardous drugs to the infusion area?

Yes, you have to wear appropriate PPE at all times when you are at risk of being exposed to a hazardous drug. There are some exceptions. Some drugs when in their final dosing forms may fall outside of <800> restrictions and may not require full PPE. A risk assessment needs to be done on each hazardous drug to determine if this is appropriate or not.

When working with hazardous drugs, double gloves need to be worn. Do both pairs of gloves need to be sterile and made of the same material?

If you are doing sterile hazardous drug compounding, then yes, both pairs of gloves need to be sterile. For non-sterile hazardous drug compounding, the gloves do not need to be sterile. All gloves need to follow USP <800> guidelines for testing and composition: powder-free chemotherapy gloves that meet American Society for Testing and Materials (ASTM) standard D6978 (or its successor) and are inspected for defects prior to use.

Does USP <800> have any restrictions on the use of sharps with hazardous drugs?

USP <800> does not have any restrictions or guidelines on the use of sharps with hazardous drugs. Caution should be exercised and precautions used to prevent exposure. A risk assessment of the technique used should be done to make sure the risk of exposure (e.g. puncture, cuts, etc.) is minimized or eliminated. Sharp containers should be easily accessible within the C-PEC during a procedure requiring the use of sharps. Note: sharp waste that has been exposed to hazardous drugs needs to be disposed of properly, and not mixed with non-hazardous drug sharp waste.

Is it okay to prepare hazardous drugs in the same Class II Type B2 biosafety cabinet where biologicals preparation occurs?

Hazardous drugs have to be prepared in their own designated biosafety cabinet (BSC) that is enclosed in a specially regulated room (at a minimum: 12 air changes per hour, exhausted outdoors through HEPA filtration, physically separated from other areas, 0.01-0.03 inches of water column negative pressure relative to surrounding rooms). You cannot use a standard biological preparation BSC for occasional hazardous drug preparation. Some non-hazardous drugs may be prepped in a hazardous drug BSC, only if the non-hazardous preparation is wrapped prior to being removed from the BSC, and all hazardous drug-appropriate PPE is worn at all times when the non-hazardous drug preparation is being handled. This is not an ideal situation.

Can the negative pressure be greater than 0.03” of water column?

No. The C-SEC, or room in which the BSC is located for hazardous drug preparation, must be between 0.01 and 0.03 inches of water column more negative than the surrounding areas.

Who is responsible for compliance?

All the personnel who may possibly come in contact with hazardous drugs are responsible for being compliant with the new USP <800> regulations. This includes all aspects of handling the drugs, from receiving to storage, compounding, administering and disposal. These regulations will be enforced by the FDA.

What precautions must be in place for the nursing staff that administer hazardous drugs to patients in an outpatient infusion setting?

All personnel who come in contact with hazardous drugs need to be fully trained. They also need to be wearing the appropriate PPE. A risk assessment should be done to determine whether a CSTD would be beneficial during the transport and administration of any hazardous drugs in this setting.

When a hazardous drug is in its final dosing product (especially tablets and capsules) and a risk assessment has been performed, may this hazardous drug fall outside of USP <800> regulations?

It may. Some hazardous drugs in specific forms, and many final dosing forms, may fall outside of USP <800> regulations. As always, a risk assessment needs to be performed prior to making this decision.

Can the hazardous drug C-SEC, or room, be accessed through an ISO Class 7 clean room where non-hazardous drug sterile compounding occurs under positive pressure?

Yes, this configuration is outlined in USP <800>, Appendix 2, and denoted to be typically used in oncology clinic settings. Both rooms need to be ISO Class 7 and have 30 ACPH (air changes per hour). This configuration has a restriction on the BUD (beyond-use date) which is outlined in Chapter <797>. As a reminder, the non-hazardous drug room is under positive pressure, and the hazardous drug room needs to be 0.01-0.03 inches of water column more negative than the non-hazardous drug room.

Do C-SECs have to have HEPA filtered external exhaust?

Yes, C-SECs (rooms) for sterile and non-sterile compounding must be externally vented through HEPA filtration.

Do non-sterile hazardous drug rooms require an ante-room?

No. Non-sterile hazardous drug C-SECs do not require an ante-room. They only require being physically separated from other areas, negative pressure of 0.01-0.03 inches of water column relative to surrounding areas, and 12 ACPH.

What are my options for storing refrigerated hazardous drugs?

Refrigerated antineoplastic hazardous drugs must be stored in their own designated refrigerator. No sharing with non-hazardous drugs is allowed. Some hazardous drugs, particularly those in their final dosing forms, may be allowed to be stored with non-hazardous drug materials, after a risk assessment has been performed.

The hazardous drug refrigerator must be in a negative pressure room with at least 12 ACPH. Examples include a storage room, buffer room, or C-SCA. You should consider an exhaust located adjacent to the refrigerator’s compressor and space behind the refrigerator in this negative pressure room.